| Project/Area Number |
21K15401
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Kagoshima University (2022-2023)
Hiroshima University (2021) |
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Principal Investigator |
NGUYEN THAO 鹿児島大学, 医歯学域歯学系, 助教 (40733837)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | cancer / cholangiocarcinoma / EPS8L3 / YAP / Hepatocellular carcinoma / SH3 domain / HCC / hepatocellular carcinoma / Hepatocellularcarcinoma / Liver cancer / Carcinogenesis |
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| Outline of Research at the Start |
Transcriptional regulator Yes-associated protein (YAP) is activated in multiple human cancers and plays critical roles in the tumor initiation, progression, metastasis, and drug resistance. Recently, we demonstrated critical role of EPS8L3 (epidermal growth factor receptor kinase substrate 8-like protein 3) in cholangiocarcinoma (CCA), a deadly form of liver cancer. In this application, we will uncover EPS8L3 as a novel oncogenic factor in CCA that maintains YAP stability and promotes YAP nuclear translocation through physical interaction in vitro and in vivo.
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| Outline of Final Research Achievements |
In this study, EPS8L3 was identified as a novel regulator of YAP that controls its stability and activity independently of the Hippo pathway. EPS8L3 was shown to physically interact with YAP and protect it from ubiquitination and proteasomal degradation. Moreover, EPS8L3 expression correlated with YAP levels and prognosis in human cancers.
These findings suggest that targeting the EPS8L3-YAP axis could potentially serve as a therapeutic strategy for YAP-dependent cancers and provide new insights into YAP regulation.
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| Academic Significance and Societal Importance of the Research Achievements |
The Hippo signaling pathway and its key effector, Yes-associated protein (YAP), play crucial roles in regulating organ size, tissue homeostasis, and cell proliferation. Dysregulation of this pathway can lead to the development and progression of various types of cancer.
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